Abstract

Stated briefly, our objectives are as follows: a) to investigate changes in drug metabolism associated with the aging process by delineating the relative importance and interrelationships of selected pathways (e.g., dealkylation, hydroxylation, glucuronidation) in older persons taking specific (model) benzodiazepines selected to illuminate each pathway. Younger adults will be studied for comparative purposes; b) to determine blood levels for bqnzodiazepines in patients receiving emergency room care for benzodiazepine overdosage; to assess the relationship between blood levels and morbidity; and to evaluate the usefulness of these levels for clinical care and treatment planning; c) to continue our studies of drug interactions; d) to investigate the development of tolerance (physiological) to benzodiazepines by studying changing threshholds to amobarbital-induced bilateral gaze nystagmus in subjects taking benzodiazepines for varying amounts of time; e) to continue to improve the practicing clinician's understanding of rational therapeutic approaches by extending our educational efforts in clinical psychopharmacology.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH034223-09
Application #
3375513
Study Section
(TDAB)
Project Start
1979-09-15
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
9
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Tufts University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111

  Publications

Warrington, Jill S; Greenblatt, David J; von Moltke, Lisa L (2004) Age-related differences in CYP3A expression and activity in the rat liver, intestine, and kidney. J Pharmacol Exp Ther 309:720-9
Greenblatt, David J; Von Moltke, Lisa L; Giancarlo, Gina M et al. (2003) Human cytochromes mediating gepirone biotransformation at low substrate concentrations. Biopharm Drug Dispos 24:87-94
Bertelsen, Kirk M; Venkatakrishnan, Karthik; Von Moltke, Lisa L et al. (2003) Apparent mechanism-based inhibition of human CYP2D6 in vitro by paroxetine: comparison with fluoxetine and quinidine. Drug Metab Dispos 31:289-93
Tran, Thanh Huu; Von Moltke, Lisa L; Venkatakrishnan, Karthik et al. (2002) Microsomal protein concentration modifies the apparent inhibitory potency of CYP3A inhibitors. Drug Metab Dispos 30:1441-5
Stormer, Elke; von Moltke, Lisa L; Perloff, Michael D et al. (2002) Differential modulation of P-glycoprotein expression and activity by non-nucleoside HIV-1 reverse transcriptase inhibitors in cell culture. Pharm Res 19:1038-45
Perloff, Michael D; von Moltke, Lisa L; Greenblatt, David J (2002) Fexofenadine transport in Caco-2 cells: inhibition with verapamil and ritonavir. J Clin Pharmacol 42:1269-74
Olubodun, Joel O; Ochs, Hermann R; Truten, Volker et al. (2002) Zolpidem pharmacokinetic properties in young females: influence of smoking and oral contraceptive use. J Clin Pharmacol 42:1142-6
Laurijssens, Bart E; Greenblatt, David J (2002) Effect of 7-day exposure to midazolam on electroencephalogram pharmacodynamics in rats: a model to study multiple pharmacokinetic-pharmacodynamic relationships in individual animals. J Pharm Pharmacol 54:77-86
Warrington, Jill S; Von Moltke, Lisa L; Shader, Richard I et al. (2002) In vitro biotransformation of sildenafil (Viagra) in the male rat: the role of CYP2C11. Drug Metab Dispos 30:655-7
Venkatakrishnan, Karthik; Von Moltke, Lisa L; Greenblatt, David J (2002) Evaluation of Supermix as an in vitro model of human liver microsomal drug metabolism. Biopharm Drug Dispos 23:183-90

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